Special Issue "Re-Irradiation, Chemotherapy, New Drugs for the (Re)-Treatment of Recurrent Gliomas"

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A special issue of Cancers (ISSN 2072-6694).

Deadline for manuscript submissions: closed (30 November 2011)

Special Issue Editor

Guest Editor
Dr. Brigitta G. Baumert (Website)

Department of Radiation-Oncology, MediClin Robert Janker Clinic & University of Bonn Med. Centre, Cooperation Unit Neurooncology, Bonn, Germany
Interests: CNS tumors; sarcomas; pet imaging; new MRI imaging techniques introduced for radiation therapy; new international trials in primary and secondary brain tumors

Special Issue Information

Dear Colleagues,

Gliomas account for ca. 70% of all primary brain tumors. Malignant glioma include all glioma with a WHO grade III and IV where the glioblastoma multiforme (WHO IV) is the most malignant and common tumour (ca. 60%). For glioblastoma, combined postoperative chemoradiotherapy with temozolomide is the current standard medical practice after results of the joint EORTC-NCIC phase III study randomizing between radiotherapy alone and combined chemoradiotherapy with temozolomide showed a significant improvement in 2-years survival from 8% to 24% for the combined treatment arm and is associated with 5 year survival estimates in the region of 10% [1,2]. It was shown, that survival favoured combined primary treatment despite salvage treatments given. However, a large proportion of patients relapse within 18 months after first treatment. Also many patients harbouring an anaplastic glioma experience either a transformation of the glioma into a higher grade or a local recurrence after primary treatment. Currently, there is no standard salvage treatment at recurrence defined. Re-treatments considered are  re-resection, second line chemotherapy or novel agents or re-irradiation.

Challenges for second line chemotherapy are fact that many patients have reduced bone marrow capacity after first line chemotherapy as well as the fact that in a subgroup of patients who responded well to temozolomide at first line treatment, developed resistance mechanisms to temozolomide at relapse. (Re)-resection cannot be curable due to the highly invasive nature of glioma cells into surrounding normal tissue. Re-irradiation carries concerns of late toxicity. New drugs with anti-angiogenic characteristsics for example of other targeted drugs open new doors for potential treatment combinations.

Future treatment approaches point into the direction of combined multi-disciplinary treatment approaches like in the primary situation. Recurrent glioma also open the possibility to testing new treatments and new treatment techniques within prospective controlled trials also as these patients are best treated within clinical trials.

These edition shall collect and present the current available knowledge on re-treatment options as well as potential future developments and current research.

For this issue and in regard to the malignant glioma, possible topics of interest may include:

Retreatment approaches either with a single treatment option like second line chemotherapy, re-operation, re-irradiation or new targeted drugs or new combined multi-disciplinary approaches combining for example, targeted drugs with irradiation or vaccination with operation, application of new imaging techniques like PET imaging or new functional MRI imaging (perfusion, diffusion) etc.

Regarding new treatment techniques, stereotactic radiotherapy, brachytherapy, proton therapy, carbion therapy, new neurosurgical techniques or current reserach on new targeted drugs, vaccination or immunotherapy for example, are of interest.

Regarding cancer biology, possible topics of interest may include cancer stem cells, resistance to MGMT, new potential targets in malignant glioma.

Regarding clinical outcome survival, local control either clincally or radiologically, toxicity, morbidity, and efficay are topics of interest.

Dr. Brigitta Baumert PhD
Guest Editor

References:

1. Stupp, R.; Mason, W.P.; van den Bent, M.J.; Weller, M.; Fisher, B.; Taphoorn, M.J.; Belanger, K.; Brandes, A.A.; Marosi, C.; Bogdahn, U.; Curschmann, J.; Janzer, R.C.; Ludwin, S.K.; Gorlia, T.; Allgeier, A.; Lacombe, D.; Cairncross, J.G.; Eisenhauer, E.; Mirimanoff, R.O.; European Organisation for Research and Treatment of Cancer Brain Tumor and Radiotherapy Groups; National Cancer Institute of Canada Clinical Trials Group. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N. Engl. J. Med. 2005, 352, 987-996.

2. Stupp, R.; Hegi, M.E.; Mason, W.P.; van den Bent, M.J.; Taphoorn, M.J.B.; Janzer, R.C.; Ludwin, S.K.; Allgeier, A.; Fisher, B.; Belanger, K.; Hau, P.; et al. on behalf of the European Organisation for Research and Treatment of Cancer Brain Tumour and Radiation Oncology Groupsthe National Cancer Institute of Canada Clinical Trials Group. Effects of radiotherapy with concomitant and adjuvant temozolomide versus radiotherapy alone on survival in glioblastoma in a randomised phase III study: 5-year analysis of the EORTC-NCIC trial. Lancet Oncol. 2009, 10, 459-466.

Submission

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. Papers will be published continuously (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are refereed through a peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Cancers is an international peer-reviewed Open Access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 800 CHF (Swiss Francs).

Keywords

  • malignant glioma
  • recurrence
  • re-irradiation
  • re-treatment
  • re-operation
  • targeted drugs

Published Papers (4 papers)

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Research

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Open AccessArticle Diagnostic Value of 11C-Methionine (MET) and 18F-Fluorothymidine (FLT) Positron Emission Tomography in Recurrent High-Grade Gliomas; Differentiation from Treatment-Induced Tissue Necrosis
Cancers 2012, 4(1), 244-256; doi:10.3390/cancers4010244
Received: 18 January 2012 / Revised: 20 February 2012 / Accepted: 22 February 2012 / Published: 1 March 2012
Cited by 6 | PDF Full-text (1960 KB) | HTML Full-text | XML Full-text
Abstract
We retrospectively evaluated the usefulness of combined measurement of L-methyl-[11C]methionine (MET) and 3'-deoxy-3'-[18F]fluorothymidine (FLT) positron emission tomography (PET) in the differential diagnosis between recurrent gliomas and necrotic lesions. Twenty-one patients with high-grade glioma, previously treated with surgery and radiotherapy with chemotherapy and first radiological suspicion of recurrence were enrolled. The uptake was assessed by the maximum standardized uptake value (SUVmax) and lesion-to-normal tissue count density ratio (L/N ratio). Of the 21 lesions, 15 were diagnosed recurrent gliomas and six were necrotic lesions. The average SUVmax was not significantly different between recurrent gliomas and necrotic lesions on either MET-PET or FLT-PET. The average L/N ratio of recurrent gliomas (3.36 ± 1.06) was significantly higher than that of necrotic lesions (2.18 ± 0.66) on MET-PET (p < 0.01) and the average L/N ratio of recurrent gliomas (7.01 ± 2.26) was also significantly higher than that of necrotic lesions (4.60 ± 1.23) on FLT-PET (p < 0.01). ROC curve analysis showed that the areas under the curves were high but not different between MET- and FLT-PET. PET studies using MET and FLT are useful in the differentiation of recurrent glioma from treatment-induced necrotic lesion. However, there is no complementary information in the differentiation with simultaneous measurements of MET- and FLT-PET. Full article

Review

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Open AccessReview External Beam Radiotherapy of Recurrent Glioma: Radiation Tolerance of the Human Brain
Cancers 2012, 4(2), 379-399; doi:10.3390/cancers4020379
Received: 2 March 2012 / Revised: 23 March 2012 / Accepted: 29 March 2012 / Published: 5 April 2012
Cited by 5 | PDF Full-text (244 KB) | HTML Full-text | XML Full-text
Abstract
Malignant gliomas relapse in close proximity to the resection site, which is the postoperatively irradiated volume. Studies on re-irradiation of glioma were examined regarding radiation-induced late adverse effects (i.e., brain tissue necrosis), to obtain information on the tolerance dose and [...] Read more.
Malignant gliomas relapse in close proximity to the resection site, which is the postoperatively irradiated volume. Studies on re-irradiation of glioma were examined regarding radiation-induced late adverse effects (i.e., brain tissue necrosis), to obtain information on the tolerance dose and treatment volume of normal human brain tissue. The studies were analyzed using the linear-quadratic model to express the re-irradiation tolerance in cumulative equivalent total doses when applied in 2 Gy fractions (EQD2cumulative). Analysis shows that the EQD2cumulative increases from conventional re-irradiation series to fractionated stereotactic radiotherapy (FSRT) to LINAC-based stereotactic radiosurgery (SRS). The mean time interval between primary radiotherapy and the re-irradiation course was shortened from 30 months for conventional re-irradiation to 17 and 10 months for FSRT and SRS, respectively. Following conventional re-irradiation, radiation-induced normal brain tissue necrosis occurred beyond an EQD2cumulative around 100 Gy. With increasing conformality of therapy, the smaller the treatment volume is, the higher the radiation dose that can be tolerated. Despite the dose escalation, no increase in late normal tissue toxicity was reported. On basis of our analysis, the use of particle therapy in the treatment of recurrent gliomas, because of the optimized physical dose distribution in the tumour and surrounding healthy brain tissue, should be considered for future clinical trials. Full article
Open AccessReview Radiation Therapy for the Treatment of Recurrent Glioblastoma: An Overview
Cancers 2012, 4(1), 257-280; doi:10.3390/cancers4010257
Received: 7 January 2012 / Revised: 1 March 2012 / Accepted: 5 March 2012 / Published: 7 March 2012
Cited by 7 | PDF Full-text (234 KB) | HTML Full-text | XML Full-text
Abstract
Despite the therapeutic advances in neuro-oncology, most patients with glioblastoma ultimately experience local progression/relapse. Re-irradiation has been poorly viewed in the past, mainly due to the overestimated risk of side effects using conventional radiotherapy. To date, thanks to the improvement of several [...] Read more.
Despite the therapeutic advances in neuro-oncology, most patients with glioblastoma ultimately experience local progression/relapse. Re-irradiation has been poorly viewed in the past, mainly due to the overestimated risk of side effects using conventional radiotherapy. To date, thanks to the improvement of several delivery techniques, together with improved imaging capabilities, re-irradiation is a viable salvage treatment option to manage such clinical scenario. A literature overview on the feasibility and efficacy of the different irradiation modalities for recurrent glioblastoma along with considerations on areas of improvement are provided. Full article
Open AccessReview Fotemustine: A Third-Generation Nitrosourea for the Treatment of Recurrent Malignant Gliomas
Cancers 2012, 4(1), 77-87; doi:10.3390/cancers4010077
Received: 7 December 2011 / Revised: 17 January 2012 / Accepted: 18 January 2012 / Published: 1 February 2012
Cited by 6 | PDF Full-text (109 KB) | HTML Full-text | XML Full-text
Abstract
Malignant gliomas account for approximately 60% of all primary brain tumors in adults. The prognosis for patients with malignant glioma has not changed significantly in recent years. Despite debulking surgery, radiotherapy and cytotoxic chemotherapy, the median survival time is nine to 12 [...] Read more.
Malignant gliomas account for approximately 60% of all primary brain tumors in adults. The prognosis for patients with malignant glioma has not changed significantly in recent years. Despite debulking surgery, radiotherapy and cytotoxic chemotherapy, the median survival time is nine to 12 months, and very few, if any, patients are cured from this illness. Fotemustine is an alkylating agent characterized by the grafting of a phosphonoalanine group onto the nitrosourea radical with consequent high lipophilicity and improved diffusion through the cell membrane and the blood-brain barrier. Fotemustine has been registered for use in two indications: disseminated malignant melanoma, including cerebral metastases, and primary brain tumors. Fotemustine is currently used in Europe, particularly in France and Italy, as a salvage therapy for recurrent malignant gliomas. Myelosuppression, leucopenia and thrombocytopenia are the most frequent side effects of treatment with fotemustine. The objective response to this treatment is between 26% and 70%, and the reported median survival time is 10 months. New drug combinations containing fotemustine and angiogenesis inhibitors, such as bevacizumab, are currently under development. In this review, we describe all the combinations of fotemustine currently used in clinical practice for recurrent malignant gliomas. Full article

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